LAUSR

Abstract Capillarisin is a naturally isolated chromone, which is one of the major bioactive constituents of Artemisia capillaries. Capillarisin has antioxidant, anti‐inflammatory, and anti‐tumor potential, but the underlying molecular mechanisms remain largely unclear. In the present study, we demonstrate that the transcription factor nuclear factor E2‐related factor‐2 (Nrf2) is activated by capillarisin in neuroblastoma SH‐SY5Y cells and microglial BV2 cells. Capillarisin leads to Nrf2 phosphorylation, subsequent activation of antioxidant response element (ARE)‐mediated transcription, and up‐regulation of downstream molecules, such as heme oxygenase‐1 (HO‐1) and NAD(P)H:quinone oxidoreductase 1. Capillarisin protects SH‐SY5Y cells from 6‐hydroxydopamine‐induced oxidative stress and attenuates inflammatory responses in lipopolysaccharide‐treated BV2 cells. The cytoprotective and anti‐inflammatory effects of capillarisin are significantly abolished in cells transfected with specific Nrf2 or HO‐1 siRNA, suggesting that these pharmacological properties of capillarisin are primarily due to increased HO‐1 activity. Capillarisin induces the activation of c‐Jun N‐terminal kinase in SH‐SY5Y and BV2 cells, which is responsible for Nrf2 phosphorylation and HO‐1 upregulation. Together, this study demonstrates that capillarisin is a potential activator of the Nrf2/ARE‐dependent pathway and could be an attractive candidate for the regulation of oxidative stress and inflammatory responses in the brain. HighlightsCapillarisin activates Nrf2/ARE/HO‐1 signaling in neural and microglial cells.JNK activation is responsible for Nrf2 phosphorylation.Capillarisin protects SH‐SY5Y neuronal cells from 6‐OHDA‐induced oxidative damage.Capillarisin inhibits LPS‐induced inflammatory responses in BV2 microglial cells.Capillarisin may combat oxidative stress and inflammatory responses in the brain.